ABSTRACT IMRT is being increasingly used for treatment of prostate cancer. In practice, however, the beam orientations used for the treatments are still selected empirically, without any guideline. The purpose of this work was to investigate interpatient variation of the optimal beam configuration and to facilitate intensity modulated radiation therapy (IMRT) prostate treatment planning by proposing a set of beam orientation class-solutions for a range of numbers of incident beams. We used fifteen prostate cases to generate the beam orientation class-solutions. For each patient and a given number of incident beams, a multiobjective optimization engine was employed to provide optimal beam directions. For the fifteen cases considered, the gantry angle of any of the optimized plans were all distributed within a certain range The angular distributions of the optimal beams were analyzed and the most selected directions are identified as optimal directions. The optimal directions for all patients are averaged to obtain the class-solution. The class-solution gantry angles for prostate IMRT were found to be: three beams (0 degrees, 120 degrees, 240 degrees), five beams (35 degrees, 110 degrees, 180 degrees, 250 degrees, 325 degrees), six beams (0 degrees, 60 degrees, 120 degrees, 180 degrees, 240 degrees, 300 degrees), seven beams (25 degrees, 75 degrees, 130 degrees, 180 degrees, 230 degrees, 285 degrees, 335 degrees), eight beams (20 degrees, 70 degrees, 110 degrees, 150 degrees, 200 degrees, 250 degrees, 290 degrees, 340 degrees), and nine beams (20 degrees, 60 degrees, 100 degrees, 140 degrees, 180 degrees, 220 degrees, 260 degrees, 300 degrees, 340 degrees). The level of validity of the class-solutions was tested using an additional clinical prostate case by comparing with the individually optimized beam configurations. The difference between the plans obtained with class-solutions and patient-specific optimizations was found to be clinically insignificant.

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Beam angle optimization (BAO) by far remains an important and challenging problem in external beam radiation therapy treatment planning. Conventional BAO algorithms discussed in previous studies all focused on photon-based therapies. Impact of BAO on proton therapy is important while proton therapy increasingly receives great interests. This study focuses on potential benefits of BAO on intensity-modulated proton therapy (IMPT) that recently began available to clinical cancer treatment.
The authors have developed a novel uncertainty incorporated BAO algorithm for IMPT treatment planning in that IMPT plan quality is highly sensitive to uncertainties such as proton range and setup errors. A linear programming was used to optimize robust intensity maps to scenario-based uncertainties for an incident beam angle configuration. Unlike conventional intensity-modulated radiation therapy with photons (IMXT), the search space for IMPT treatment beam angles may be relatively small but optimizing an IMPT plan may require higher computational costs due to larger data size. Therefore, a deterministic local neighborhood search algorithm that only needs a very limited number of plan objective evaluations was used to optimize beam angles in IMPT treatment planning.
Three prostate cancer cases and two skull base chordoma cases were studied to demonstrate the dosimetric advantages and robustness of optimized beam angles from the proposed BAO algorithm. Two- to four-beam plans were optimized for prostate cases, and two- and three-beam plans were optimized for skull base cases. By comparing plans with conventional two parallel-opposed angles, all plans with optimized angles consistently improved sparing at organs at risks, i.e., rectum and femoral heads for prostate, brainstem for skull base, in either nominal dose distribution or uncertainty-based dose distributions. The efficiency of the BAO algorithm was demonstrated by comparing it with alternative methods including simulated annealing and genetic algorithm. The numbers of IMPT plan objective evaluations required were reduced by up to a factor of 5 while the same optimal angle plans were converged in selected comparisons.
Uncertainty incorporated BAO may introduce pronounced improvement of IMPT plan quality including dosimetric benefits and robustness over uncertainties, based on the five clinical studies in this paper. In addition, local search algorithms may be more efficient in finding optimal beam angles than global optimization approaches for IMPT BAO.

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This Idea Award (DAMD17-03-1-0023, entitled "Intensity Modulated Radiation Treatment of Prostate Cancer Guided by High Field MR Spectroscopic Imaging") was awarded to the principal investigator (PI) for the period of May 1, 2003 - April 30, 2006. This is the final report for the grant. The goal of this project is to establish biologically conformal -- as opposed to anatomically conformal -- IMRT as a viable modality through integration with 3T magnetic resonance spectroscopic imaging (MRSI) to more effectively kill prostate tumor cells. The underlying hypothesis driving this work is that the MRSI-guided IMRT will provide substantially improved dose distributions required to achieve greater local tumor control while maintaining, or reducing, complications to sensitive structures. The specific aims of the project are: (1) To establish a robust procedure for registering and mapping of MR spectroscopic data to CT/MRI images for prostate irradiation. (2) To develop an inverse planning system for MRSI-guided IMRT prostate treatment and demonstrate the feasibility of concurrent dose escalation to intraprostatic lesion(s) through a set of phantom studies and at least two previously treated prostate cases who had undergone CT/MRSI scans. Under the generous support from the U.S. Army Medical Research and Materiel Command (AMRMC), the PI has contributed significantly to prostate cancer research by applying physics and engineering knowledge to prostate cancer research. A number of significant conference abstracts and refereed papers have resulted from the support. The preliminary data obtained under the support of the grant has also enabled the PI to start new research initiatives, in particularly, in adaptive prostate radiation therapy. The past year's research activities of the PI are highlighted in the following.

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Intensity-Modulated Radiation Therapy is the technique of delivering radiation to cancer patients by using non-uniform radiation fields from selected angles, with the aim of reducing the intensity of the beams that go through critical structures while reaching the dose prescription in the target volume. Two decisions are of fundamental importance: to select the beam angles and to compute the intensity of the beams used to deliver the radiation to the patient. Often, these two decisions are made separately: first, the treatment planners, on the basis of experience and intuition, decide the orientation of the beams and then the intensities of the beams are optimized by using an automated software tool. Automatic beam angle selection (also known as Beam Angle Optimization) is an important problem and is today often based on human experience. In this context, we face the problem of optimizing both the decisions, developing an algorithm which automatically selects the beam angles and computes the beam intensities. We propose a hybrid heuristic method, which combines a simulated annealing procedure with the knowledge of the gradient. Gradient information is used to quickly find a local minimum, while simulated annealing allows to search for global minima. As an integral part of this procedure, the beam intensities are optimized by solving a Linear Programming model. The proposed method presents a main difference from previous works: it does not require to have on input a set of candidate beam angles. Indeed, it dynamically explores angles and the only discretization that is necessary is due to the maximum accuracy that can be achieved by the linear accelerator machine. Experimental results are performed on phantom and real-life case studies, showing the advantages that come from our approach.

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